The experiments in the chronic sheep lung lymph preparation using the large molecular weight fraction are now being done, 5-10 studies are planned in 5-10 sheep. These experiments will be continued for 8-12 hours of observation to look for a delayed second phase reaction as it is seen with gram negative endotoxin. Once the physiologic effects are defined in this preparation, pharmacological blockade of the reaction with indomethacin, diphenhydramine and methysergide will be attempted. The mediators of the response could then be explored, either by selective blockade with the above compounds or by measurements of lung release of prostaglandins, in blood and lung lymph. Fractionation of the large molecular weight fraction will be done, by exposure to low pH and the small fragments compared to those found in the early experiments. The active fraction will be studied and its structure defined. Radioactive tagging will be used to sort out the target organs. Chemically altered bacterial components will be used to attempt the prevention of the reaction by competition of the receptor sites. The studies on newborn lambs will be continued, using the large molecular weight fraction. Multiple indicator dilution methods will be used primarily to look at lung water content and pulmonary capillary permeability. The helium rebreathing method will be used to measure functional residual capacity and tidal volume, transpulmonary pressure and pulmonary compliance will be measured with a Hewlett-Packard respiratory integrator. Hematologic studies will include white blood cell and differential counts and platelet counts.